GPI 6150, a poly (ADP-ribose) polymerase inhibitor, exhibits an anti-inflammatory effect in rat models of inflammation

Eur J Pharmacol. 2001 Mar 9;415(1):85-94. doi: 10.1016/s0014-2999(01)00809-3.

Abstract

Poly (ADP-ribose) polymerase, a nuclear enzyme activated by DNA strand breaks, has been show to play an important role in the pathogenesis of inflammation. Here, we investigate the effects of GPI 6150 (1,11b-dihydro-[2H]benzopyrano [4,3,2-de]isoquinolin-3-one), a new poly (ADP-ribose) polymerase inhibitor, in animal models of acute and chronic inflammation (carrageenan-induced paw edema, adjuvant-induced arthritis and zymosan-induced multiple organ failure) where oxygen radicals, nitric oxide and peroxynitrite are known to play a crucial role in the inflammatory process. The results show that the poly (ADP-ribose) polymerase inhibitor GPI 6150 inhibits the inflammatory response (paw swelling, and organ injury). The present results demonstrate that inhibition of poly (ADP-ribose) polymerase by GPI 6150 exerts potent anti-inflammatory effects. Part of these anti-inflammatory effects may be related to a reduction of neutrophil recruitment into the inflammatory site.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Arthritis, Experimental / prevention & control
  • Benzopyrans / pharmacology*
  • Carrageenan / administration & dosage
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Edema / chemically induced
  • Edema / prevention & control
  • Enzyme Inhibitors / pharmacology*
  • Hindlimb
  • Inflammation / chemically induced
  • Inflammation / mortality
  • Inflammation / prevention & control*
  • Isoquinolines / pharmacology*
  • Liver / drug effects
  • Liver / pathology
  • Lung / drug effects
  • Lung / pathology
  • Male
  • Poly(ADP-ribose) Polymerase Inhibitors*
  • Poly(ADP-ribose) Polymerases / metabolism
  • Rats
  • Rats, Long-Evans
  • Survival Rate
  • Zymosan / administration & dosage

Substances

  • Anti-Inflammatory Agents
  • Benzopyrans
  • Enzyme Inhibitors
  • GPI 6150
  • Isoquinolines
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Carrageenan
  • Zymosan
  • Poly(ADP-ribose) Polymerases